Phenotype of the Obese Koletsky (f) Rat Due to Tyr763Stop Mutation in the Extracellular Domain of the Leptin Receptor (Lepr): Evidence for Deficient Plasma-to-CSF Transport of Leptin in Both the Zucker and Koletsky Obese Rat
| Autor: | Rudolph L. Leibel, X. Sharon Wu-Peng, Margery Nicolson, Shun Mei Liu, Norichika Okada, Streamson C. Chua |
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| Rok vydání: | 1997 |
| Předmět: |
Leptin
medicine.medical_specialty Genotype Endocrinology Diabetes and Metabolism Mutant Nonsense mutation Receptors Cell Surface Biology medicine.disease_cause Polymerase Chain Reaction Rats Mutant Strains Cerebrospinal fluid Internal medicine Internal Medicine medicine Extracellular Animals Point Mutation Obesity DNA Primers Mutation Leptin receptor Brain Proteins Null allele Rats Rats Zucker Phenotype Endocrinology Receptors Leptin Tyrosine Carrier Proteins |
| Zdroj: | Diabetes. 46:513-518 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | The obese phenotypes of the diabetes ( db ) mouse and fatty ( fa ) rat are due to functional null mutations of the leptin receptor (Lepr). The recessive mutation in the Koletsky ( f ) obese rat maps to the same genetic intervals as db and fa and fails to complement the fa mutation. Comparison of the sequence of brain Lepr cDNA from +/+ and f / f animals reveals a T2349A transversion resulting in a Tyr763Stop nonsense mutation in the gene just before the transmembrane domain. Virtual absence of Lepr mRNA in whole brain from f / f animals is consistent with the presence of a null mutation. The predicted reduced cerebrospinal fluid (CSF) transport of leptin in both f / f and fa / fa mutants is reflected in the ∼10-fold lower ratio of CSF/plasma leptin concentration in the obese versus lean animals. However, equivalent CSF leptin concentration between lean and obese rats ( fa / fa , f / f ) indicates that leptin can enter the CSF through a non–Lepr-mediated mechanism, which may be saturated at normal physiological plasma leptin concentration. |
| Databáze: | OpenAIRE |
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